Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 21, Issue 2, Pages 153-160Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2009.03.010
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Funding
- Cancer Research Institute Investigator award
- Marie Curie International Reintegration Grant (IRG)
- Howard Hughes Medical Institute
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Differentiation of T(H)1 and T(H)2 effector cells proceeds through several phases: First, naive CD4(+) precursor cells are instructed to differentiate as appropriate to optimally fight the infectious threat encountered. This process is governed by the IL12 and IL4 cytokines, as well as by signaling through the Notch receptor. In response to these signals, transcription is initiated of lineage specific cytokine genes including the Ifn gamma and 114 genes as well as of genes encoding transcriptional regulators, such as T-bet and Gata3. The respective differentiation programs are reinforced by both positive and negative feedback mechanisms. Furthermore, epigenetic modifications of the lineage specific genes result in the emergence of regulatory elements, which control high level lineage restricted expression by both intrachromosomal and interchromosomal associations. Together, these mechanisms ensure stable inheritance of the differentiated fate in the numerous progeny of the original naive CD4(+) T cells.
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